As the HIV epidemic has evolved in the U.S., the picture of pediatric HIV is changing. With our success in PACTG #076, we have reduced the overall national mother-child transmission rate to less than 5%. Consequently, we rarely see newly infected infants. When we do identify an infected infant, however, it is often because its mother was not tested for HIV or did not received prenatal care. Other changes include the success of combination antiretroviral therapy (ART), which has allowed HIV to become a chronic disease. With long-term therapy, behavioral issues including adherence to therapy have become important determinants of the success of ART. Other issues related to long-term survival of infected children have become increasingly important. These include the short and long-term toxicity of ART (for both infected and uninfected but exposed infants), and the effects of HIV -infection and therapy on growth and development, metabolic and lipid abnormalities, neurological and psychological development, and reproductive status, including the potential for genetic effects in the offspring of our patients. Another major change has been an alarming increase in the number of HIV-infected adolescents, who acquire their infections by sexual transmission or parenteral drug use. This has proven to be a particularly challenging population to identify, treat, and enroll into studies. The scientific agenda of the PACTG has responded to these changes, as reflected in the PACTG Group application headed by Dr. Spector. This proposal will allow the Tulane/LSU Pediatric AIDS Clinical Trials Unit (PACTU) to contribute to the new PACTG scientific agenda. As the only PACTU within a 325 mile radius of New Orleans, we have served children, adolescents, and families in the region since 1992. We represent a collaboration between the Tulane and LSU Health Sciences Centers, with case management and social service support provided by FACES. In order to expand our outreach, we have recently established an ancillary site in Baton Rouge, LA, at the Earl K. Long Charity Hospital. We propose to participate in pediatric, adolescent, and perinatal trials, including long-term studies of the complications of HIV infection and antiretroviral therapy. We will utilize the GCRC to conduct phase I studies of new agents in children and pregnant women. We have established an extremely successful adolescent program, and plan to collaborate with the local ATN site and the RAP social services program of FACES. We are participating in the MIRIAD study of rapid HIV testing of women in labor with unknown serostatus and plan to introduce this protocol into the PACTU. Finally, we will continue to provide leadership in the areas of perinatal transmission of HIV, the complications of HIV infection, adolescent medicine, and behavioral issues such as adherence to therapy.